Akademik Veri Yönetim Sistemi
Yükseköğretim Kurumları Destekli Proje, 2017 - 2018
Ovarian cancer is the fifth cancer type which is the cause of women deaths worldwide. Epithelial ovarian cancer (EOC) is the most lethal ovarian cancer type, is usually asymptomatic, and few screening tests are available. Early detection of EOC has great importance in the clinic. EOC shows itself at the rate of approximately %70 on the advanced-stage and less than 30% of these patients may continue their life for 5 years more. In contrast, the 5-year survival rate of patients diagnosed in stage I is 90% and the 5-year survival rate of patients diagnosed in stage II is up to 70%.
Since observing of cancer mass and biopsy are difficult in the early stages, diagnosis by noninvasive methods are getting more and more important nowadays. Therefore, the detection of tumor materials (in circulating tumor cells, free nucleic acids, and exosomes) passed to body fluids in the first stage of cancer can make possible the early diagnosis of cancer. If the materials obtained by the method, called liquid biopsy, are proven to be specific to ovarian cancer, they can be used as more objective and comparable potential serum biomarkers. In recent years, one of the most studied serum biomarkers is microRNAs (miRNAs) which are non-coding short RNAs family and also regulate gene expression by targeting mRNAs. Unlike health individuals, as having the expression variability according to the disease, the patient and the stage of the disease, miRNAs have the potential biomarker in early detection of many diseases and especially cancer, including EOC. The studies on EOC in recent years have focused on the creation of miRNA expression profiling and the identification of miRNAs derived from peripheral blood as new biomarkers in circulation.
The biomarker potentials of 4 candidate miRNAs (hsa-miR-885-5p, hsa-let-7d-3p, hsa-miR-548am- 5p, hsa-miR-1909-5p), whose expression levels have been determined as different using microarray by comparing serum samples of healthy individuals with the serum of EOC patients in the same age range as were investigated in this thesis. Microarray data have shown that the expression of 4 miRNAs decreases significantly in the serum of EOC patients (p <0.05). Also, the expression of same miRNAs has been validated by Real-time PCR technique in this study. Different expressions of hsa-miR-1909-5p, hsa-miR-885-5p, hsa-let-7d-3p were statistically significant (p <0.05). It has been detected which genes and related pathways affected by the validated miRNAs using "Pathway Studio" database. An important regulator of cancer as one target genes of hsa-let-7d-3p has been identified hmga2 gene according to the database. The expression analysis of this gene, which is known related to ovarian cancer, has been performed to determine the effect of hsa-let-7d-3p on HMGA2 gene. As a result of this research, it has been suggested that hsa-miR-1909-5p, hsa-miR-548am-5p, and hsa-miR-885-5p miRNAs can be added to early diagnosis panels and be utilized as potential biomarkers. In studies to investigate the pathophysiology of EOC, the effect of hsa-let-7d-3p on the regulation of the HMGA2 gene has not been accurately determined.